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Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?

Overview
Specialty Physiology
Date 2024 Apr 30
PMID 38687468
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Abstract

High levels of oxidant stress in the form of reactive oxidant species are prevalent in the circulation and tissues in various types of cardiovascular disease including heart failure, hypertension, peripheral arterial disease, and stroke. Here we review the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an important and widespread antioxidant and anti-inflammatory transcription factor that may contribute to the pathogenesis and maintenance of cardiovascular diseases. We review studies showing that downregulation of Nrf2 exacerbates heart failure, hypertension, and autonomic function. Finally, we discuss the potential for using Nrf2 modulation as a therapeutic strategy for cardiovascular diseases and autonomic dysfunction.

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References
1.
Schieber M, Chandel N . ROS function in redox signaling and oxidative stress. Curr Biol. 2014; 24(10):R453-62. PMC: 4055301. DOI: 10.1016/j.cub.2014.03.034. View

2.
Priestley J, Fink K, McCord J, Lombard J . NRF2 activation with Protandim attenuates salt-induced vascular dysfunction and microvascular rarefaction. Microcirculation. 2019; 26(7):e12575. PMC: 7154587. DOI: 10.1111/micc.12575. View

3.
Zhang D, Hannink M . Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol. 2003; 23(22):8137-51. PMC: 262403. DOI: 10.1128/MCB.23.22.8137-8151.2003. View

4.
Kishi T, Hirooka Y, Kimura Y, Ito K, Shimokawa H, Takeshita A . Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats. Circulation. 2004; 109(19):2357-62. DOI: 10.1161/01.CIR.0000128695.49900.12. View

5.
Banks N, Rogers E, Stanhewicz A, Whitaker K, Jenkins N . Resistance exercise lowers blood pressure and improves vascular endothelial function in individuals with elevated blood pressure or stage-1 hypertension. Am J Physiol Heart Circ Physiol. 2023; 326(1):H256-H269. PMC: 11219052. DOI: 10.1152/ajpheart.00386.2023. View